Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype
Abstract Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. Ho...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2023-08-01
|
| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-023-40895-6 |
| _version_ | 1797558430455562240 |
|---|---|
| author | Ki Oh Yun Jae Yoo Luke A. Torre-Healy Manisha Rao Danielle Fassler Pei Wang Michael Caponegro Mei Gao Joseph Kim Aaron Sasson Georgios Georgakis Scott Powers Richard A. Moffitt |
| author_facet | Ki Oh Yun Jae Yoo Luke A. Torre-Healy Manisha Rao Danielle Fassler Pei Wang Michael Caponegro Mei Gao Joseph Kim Aaron Sasson Georgios Georgakis Scott Powers Richard A. Moffitt |
| author_sort | Ki Oh |
| collection | DOAJ |
| description | Abstract Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC. |
| first_indexed | 2024-03-10T17:31:19Z |
| format | Article |
| id | doaj.art-20d46bef9b454b9f8bb70caf60828d92 |
| institution | Directory Open Access Journal |
| issn | 2041-1723 |
| language | English |
| last_indexed | 2024-03-10T17:31:19Z |
| publishDate | 2023-08-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj.art-20d46bef9b454b9f8bb70caf60828d922023-11-20T10:00:32ZengNature PortfolioNature Communications2041-17232023-08-0114111310.1038/s41467-023-40895-6Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtypeKi Oh0Yun Jae Yoo1Luke A. Torre-Healy2Manisha Rao3Danielle Fassler4Pei Wang5Michael Caponegro6Mei Gao7Joseph Kim8Aaron Sasson9Georgios Georgakis10Scott Powers11Richard A. Moffitt12Department of Biomedical Informatics, Stony Brook UniversityDepartment of Biomedical Informatics, Stony Brook UniversityDepartment of Biomedical Informatics, Stony Brook UniversityDepartment of Biomedical Engineering, Stony Brook UniversityDepartment of Biomedical Informatics, Stony Brook UniversityDepartment of Cell Systems & Anatomy, University of Texas Health Science CenterDepartment of Pharmacology, Stony Brook UniversityDepartment of Surgery, University of Kentucky and Markey Cancer CenterDepartment of Surgery, University of Kentucky and Markey Cancer CenterDepartment of Surgery, Stony Brook UniversityDepartment of Surgery, Stony Brook UniversityDepartment of Pathology, Stony Brook UniversityDepartment of Biomedical Informatics, Stony Brook UniversityAbstract Bulk analyses of pancreatic ductal adenocarcinoma (PDAC) samples are complicated by the tumor microenvironment (TME), i.e. signals from fibroblasts, endocrine, exocrine, and immune cells. Despite this, we and others have established tumor and stroma subtypes with prognostic significance. However, understanding of underlying signals driving distinct immune and stromal landscapes is still incomplete. Here we integrate 92 single cell RNA-seq samples from seven independent studies to build a reproducible PDAC atlas with a focus on tumor-TME interdependence. Patients with activated stroma are synonymous with higher myofibroblastic and immunogenic fibroblasts, and furthermore show increased M2-like macrophages and regulatory T-cells. Contrastingly, patients with ‘normal’ stroma show M1-like recruitment, elevated effector and exhausted T-cells. To aid interoperability of future studies, we provide a pretrained cell type classifier and an atlas of subtype-based signaling factors that we also validate in mouse data. Ultimately, this work leverages the heterogeneity among single-cell studies to create a comprehensive view of the orchestra of signaling interactions governing PDAC.https://doi.org/10.1038/s41467-023-40895-6 |
| spellingShingle | Ki Oh Yun Jae Yoo Luke A. Torre-Healy Manisha Rao Danielle Fassler Pei Wang Michael Caponegro Mei Gao Joseph Kim Aaron Sasson Georgios Georgakis Scott Powers Richard A. Moffitt Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype Nature Communications |
| title | Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| title_full | Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| title_fullStr | Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| title_full_unstemmed | Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| title_short | Coordinated single-cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| title_sort | coordinated single cell tumor microenvironment dynamics reinforce pancreatic cancer subtype |
| url | https://doi.org/10.1038/s41467-023-40895-6 |
| work_keys_str_mv | AT kioh coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT yunjaeyoo coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT lukeatorrehealy coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT manisharao coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT daniellefassler coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT peiwang coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT michaelcaponegro coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT meigao coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT josephkim coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT aaronsasson coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT georgiosgeorgakis coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT scottpowers coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype AT richardamoffitt coordinatedsinglecelltumormicroenvironmentdynamicsreinforcepancreaticcancersubtype |